We continue to develop mathematical models of human metabolism and have conducted several validation studies using a variety of published data on the metabolic responses to overfeeding, underfeeding, and isocaloric changes in dietary macronutrients. Our models have been deployed as a clinical research tool in collaboration with NIH clinical investigators to help design prospective studies as well as plan and track clinical weight management programs. Our models are being applied to a variety of problems, from calculating the relationship between human weight change and food intake to calculating changes of free-living energy intake using frequent body weight measurements.